Erez Ely, Acuna Higaki Adrian R, Cupo Michela, Phu Tuan Anh, Verma Shiv, Assi Roland, Vallabhajosyula Prashanth
Division of Cardiac Surgery, Department of Surgery, Yale School of Medicine, New Haven, Conn.
Division of Cardiac Surgery, Department of Surgery, Yale School of Medicine, New Haven, Conn.
J Thorac Cardiovasc Surg. 2024 Sep 23. doi: 10.1016/j.jtcvs.2024.09.026.
To analyze the effectiveness of the current genetic testing guidelines for patients with thoracic aortic aneurysms.
We evaluated genetic tests for thoracic aortic disease (TAD) from 2012 to 2023 in patients aged 18 and older with a thoracic aorta diameter greater than 4 cm. Mutation rates were compared by American College of Cardiology/American Heart Association testing criteria met by patients: age younger than 60 years, syndromic features of connective tissue diseases (CTDs), family history, or none. Results were classified as pathogenic, variants of uncertain significance (VUS), or negative. Genes tested were analyzed in 2 categories: primary (strongly associated with heritable diseases) or secondary (less strongly associated).
In total, 1034 patients were included: 42.4% aged younger than 60 years, 19.1% with syndromic features of CTD, 41.8% with family history, and 30.7% meeting no criteria. Overall, 3.97% had pathogenic mutations, and 27.27% had VUS. Mutation rates were greatest in patients with syndromic features of CTD (13.2%), followed by patients aged younger than 60 years (5.48%), with a family history (4.63%), and with no criteria met (2.21%). Primary genes had pathogenic mutation rates of 3.29% and VUS rates of 12.19%. Secondary genes had lower pathogenic rates (0.68%) but greater VUS (17.5%). Mutation rates in primary genes peaked at 22% in patients meeting all criteria, whereas those younger than 60 years without family history or syndromic features of CTD had the lowest rate (0.54%).
Refining genetic testing guidelines to incorporate multiple patient criteria could enhance risk stratification and support informed decision-making in genetic testing for TAD. Limiting testing to genes strongly associated with TAD could lower VUS rates.
分析当前胸主动脉瘤患者基因检测指南的有效性。
我们评估了2012年至2023年期间，年龄在18岁及以上、胸主动脉直径大于4厘米的胸主动脉疾病（TAD）患者的基因检测情况。根据患者符合的美国心脏病学会/美国心脏协会检测标准比较突变率：年龄小于60岁、结缔组织病（CTD）的综合征特征、家族史或无上述情况。结果分为致病性、意义未明变异（VUS）或阴性。检测的基因分为两类进行分析：主要基因（与遗传性疾病密切相关）或次要基因（相关性较弱）。
共纳入1034例患者：42.4%年龄小于60岁，19.1%有CTD的综合征特征，41.8%有家族史，30.7%不符合任何标准。总体而言，3.97%有致病性突变，27.27%有VUS。CTD综合征特征患者的突变率最高（13.2%），其次是年龄小于60岁的患者（5.48%）、有家族史的患者（4.63%）和不符合任何标准的患者（2.21%）。主要基因的致病性突变率为3.29%，VUS率为12.19%。次要基因的致病性率较低（0.68%），但VUS率较高（17.5%）。符合所有标准患者的主要基因突变率在22%时达到峰值，而年龄小于60岁、无家族史或CTD综合征特征的患者突变率最低（0.54%）。
完善基因检测指南以纳入多个患者标准，可加强风险分层，并为TAD基因检测中的知情决策提供支持。将检测限于与TAD密切相关的基因可降低VUS率。
